The inefficient infiltration of tumors by vaccine-induced or adoptively transferred T cells remains a limiting factor in the clinical efficacy of immunotherapy. Interventions to enhance T cell access of tumors have been described; however, these approaches generally require direct intra-tumoral drug delivery or systemic conditioning with significant adverse effects, limiting their applicability. To develop a non-toxic and tumor- directed means to enhance effector cell infiltration of tumors; we collaborated with Qu Biologics (Vancouver, BC) to employ Site-Specific Immunomodulators (SSIs), a bacteria-based adjuvant therapy that mediates organ- or tissue-specific homing and accumulation of immune cells. SSI technology uses specific bacterial preparations that correlate with specific organ/tissue compartments where prior infection has likely occurred and resolved (for example, SSI from Klebsiella pneumoniae for lung, Staphylococcus aureus for skin, Escherichia coli for colon, etc.). Preliminary studies in murine models demonstrate that intradermal/subcutaneous administration of SSIs reduces B16 melanoma burden and induces interferon production in the tumor microenvironment. We hypothesize that SSI therapy may provide a novel means of inducing or restoring T cell infiltration in an organ-specific manner, thereby enhancing the efficacy of T cell-based therapeutics. In this exploratory study, we will use established and novel murine models to 1) evaluate SSI-dependent cytokine and chemokine expression in solid and metastatic-like tumors; 2) determine SSI-mediated T cell infiltration of solid and metastatic-like tumors with regard to specific chemokine receptor profiles; and 3) evaluate SSI therapy as an adjuvant for existing immunotherapeutic interventions. These models may provide readily translatable therapeutic approaches to significantly enhance the efficacy of immunotherapy by targeting T cells into tumor-burdened compartments.